Process for the manufacturing of dextro-pantothenic acid



Patented Feb. 15, 1944 PROCESS FOR THE MANUFACTURING OF.DEXTRO-PANTOTHENIO ACID Andr Griissner, Basel, Switzerland, assignor toHoflmann-La Roche, Inc., Nutley, N. J., a corporation of New Jersey NoDrawing. Application September 16, 1941, Serial No. 411,077. InSwitzerland September The resolution of pantothenic acid into theoptically pure antipodes by. fractionated crystallisation of the quininesalts has already been tried (Berichte der Deutschen ChemischenGesellschaft, vol. 73, year 1940, page 971). From the physical constantsclted inv the said publication it follows that the separation of thequinine salts of dextroand levo-pantothenic acid did not succeed.Whereas the melting point of levo-quinine pantothenate is stated to be165-167 0., it is in fact 183 C. The specific rotation of this quininesalt is -l21 and not -115. The melting point of the quinine salt ofdextro-pantothenic acid is not 148-152 0., as stated in theabovementioned publication, but 136-13'7 C.

It has now been found that the resolution of the racemic pantothenicacid by way of the quinine salts can be effected first byrecrystallisation of the quinine salt of the racemic pantothenic acidfrom ethyl alcohol. Thereby, the quinine salt of levo-pantothenic acidseparates in small'felted needles of melting point 183 C. A

further crystallisation of this salt is rendered.

possible by concentration and cooling of the mother liquor to C. Afterseparation of the greater part-of'the levo-quinine pantothenate, themother liquor contains the quinine salt of the dextro-form in highconcentration so that it .crystallises out as colorless needles ofmeltin point 136-137 C. after evaporation of the alcohol andrecrystallisation from acetone. The acetone mother liquor again containsa mixture of the dextroand levo-form. Once more pure dex- Example 54.5parts by weight of d,l-barium pantothe etc are dissolvedin 150 parts byvolume of alco- In-the.

' tro-quinine pantothenate can be obtained therefrom if the acetone isevaporated and the residue pantothenlc acid.

1 Claim. (cream-534) hol while heating. This solution is treated with ahot solution of about 77 parts by weight of quinine sulfate in 200 partsby volume of alcohol.

The clear solution freed from barium sulfate byv centrifuging containsneither barium nor sulfuric acid; it is evaporated to 200 parts byvolume and then left to stand. The precipitated crystals are sucked offafter some time. About 18 parts by weight of the quinine salt oflevo-pantothenic acid are obtained having a melting point of 183" C. anda specific rotation of [u] =121 (c=1.342 in water). mother liquor andleaving it to stand at 0 C. further quantities of'levo-quininepantothenate are separated. Altogether about 47 parts by weight of thissalt are obtained. A a

The mother liquors are then evaporated to dryness and the residuedissolved in about parts by volume of acetone whereupon the quinine saltof destropantothenic acid separates after a while in vcolorless needleshaving a melting point of -137" C. and a specific rotation of v [al =95(c=0.937 in water). The yield amounts to about 31 partsby weight. Byrepeating the process further quantities are obtained from the motherliquor. v

The dextro-quinine pantothenate is dissolved in water and renderedalkaline to phenolphthalein by means of bryta water. The precipitatedquinine is removed by shaking with chloroform and ether and the bariumprecipitated with su.l-. furic acid. After the separation of the bariumsulfate. dextro-pantothenic acid is obtained as a syrup by evaporationin vacuo.

A process for the manufacture of dextro-panto- I anmut aaiissmsn.

By concentration of the

